The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the present invention.
Technological advances in combinatorial chemistry, genomics. and proteomics have fostered an increased need for rapid high throughput (HTP) screening methods able to monitor and/or detect the reaction between one or more target species and binding partners or potential binding partners of such targets. Various systems have been, and are being, explored to detect analytes. Systems such as affinity chemical sensing, arrayed sensors, and acoustic sensors are being investigated for their respective usefulness in detecting analytes in clinical and non-clinical settings.
Affinity Chemical Sensing
Affinity chemical sensing systems attempt to detect interactions between a target analyte and an appropriate binding partner. Such systems generally rely on the production or use of a detectable signal. Affinity chemical sensing systems employ binding partners which can be discrete molecular species to which the target analyte specifically binds, or a phase, such as an organic polymer, into which the target partitions. Covalently attached labels such as, fluorescent, electrochemical, radioactive, or mass based-probes are typically employed in such systems. Methods for determining the presence analytes by using systems that detect the inherent optical, electrochemical, or physical properties of a target species or changes in the properties of the layer containing the binding partner to which a target species binds, have been employed to detect and/or monitor un-labeled analytes.
Charych, et al., U.S. Pat. No. 6,022,748, filed Aug. 29, 1997, describe an example of a sensor employing an optically active sensor coating that changes color upon binding of the target. Further example of affinity sensing methods are described by W. Lukosz, “Principles and sensitivities of integrated optical and surface plasmon sensors for direct affinity sensing and immunosensing”, Biosensors & Bioelectronics 6, 1991, pp. 215-225. Utilization of surface plasmon resonance in sensing applications is also described by Hanning in U.S. Pat. No. 5,641,640, filed Dec. 29, 1994. A Chemically Selective Field Effect Transistor (CHEMFET) that determines target binding by monitoring a signal change on the sensor surface in response to target binding to the said surface, is described by Shimada in U.S. Pat. No. 4,218,298, filed Nov. 3, 1978. Ribi et al., in U.S. Pat. Nos. 5,427,915 and 5,491,097, filed Aug. 9, 1993 and Feb. 28, 1994 respectively, describe affinity-based microfabricated sensors in which a measurable change in conductivity of a bio-electric sensor layer is used to determine binding of a target species.
Arrayed Sensors
Arrayed sensors have multiple individually addressable sites on the device surface which are modified to contain binding partners for a target molecule to be detected. An example of such a detection system can be found in U.S. Pat. No. 6,197,503, filed Nov. 26, 1997 by Vo-Dinh et al. The patent describes a device employing multiple optical sensing elements and microelectronics on a single integrated chip combined with one or more nucleic acid-based bioreceptors designed to detect optically labeled, sequence specific genetic constituents in complex samples.
Other examples of arrayed sensors include: Pinkel et al., U.S. Pat. No. 6,146,593 filed Jul. 24, 1997, describe a method for fabricating biosensors using functionalized optical fibers to create a high density array of uniquely addressable biological binding partners; Fodor et al., U.S. Pat. No. 6,124,102 filed Apr. 21, 1998 describe an optical sensor array having a planar surface derivatized with ligands of an optically active target species immobilized at known locations such that each location comprises a “pixel” of an optical read out device. These and similar devices can be successful for arrayed detection and therefore useful for parallel screening of multiple interactions where the analyte is either labeled or inherently optically, electrically, or specifically chemically active.
Acoustic Sensors
Another-field of technology having combine arrayed sensors is that of sensors based on bulk or microfabricated resonant devices. Such sensors have been demonstrated in systems used to determine 3-dimensional acceleration, speed, and position, as transducers for monitoring environmental conditions such as pressure, fluid flow, temperature, and as gravimetrically sensitive elements in chemical affinity sensors.
Acoustic sensors for chemical sensing have been demonstrated in low-density arrays in for example Ballato U.S. Pat. No. 4,596,697 filed Sep. 4, 1984 which describes surface acoustic wave (SAW) devices. Arrays of cantilever sensors for gas phase sensing of multiple analytes are described by Lang et al (Lang, H. P.; Baller, M. K.; Berger, R.; Gerber, Ch.; Gimzewski, J K.; Battiston, F M; Fornano, P.; Ramseyer, J. P.; Meyer, E.; Guntherodt, H. J.; IBM Research Report, RZ 3068 (#93114), Oct. 19, 1998), and Britton et al (Britton, C. L.; Jones, R. L.; Oden, P. I.; Hu, Z.; Warmack, R. J.; Smith, S. F.; Bryan, W. L.; Rochelle, J. M.; Ultramicroscopy, 82, 2000, p. 17-21).